Cellular and molecular connections between sleep and synaptic plasticity

Progress in Neurobiology
Volume 69, Issue 2, February 2003, Pages 71-101

Copyright © 2003 Elsevier Science Ltd. All rights reserved.

Cellular and molecular connections between sleep and synaptic plasticity

Joel H. BeningtonCorresponding Author Contact Information, E-mail The Corresponding Author, a and Marcos G. FrankE-mail The Corresponding Author, b, 1

a Department of Biology, St. Bonaventure University, St. Bonaventure, NY 14778, USA

b Department of Neuroscience, University of Pennsylvania School of Medicine, 215 Stemmler Hall, 35th Hamilton Walk, Philadelphia, PA 19104-6074, USA

Received 5 December 2002;
accepted 7 February 2003. ;
Available online 1 April 2003.

Abstract
The hypothesis that sleep promotes learning and memory has long been a subject of active investigation. This hypothesis implies that sleep must facilitate synaptic plasticity in some way, and recent studies have provided evidence for such a function. Our knowledge of both the cellular neurophysiology of sleep states and of the cellular and molecular mechanisms underlying synaptic plasticity has expanded considerably in recent years. In this article, we review findings in these areas and discuss possible mechanisms whereby the neurophysiological processes characteristic of sleep states may serve to facilitate synaptic plasticity. We address this issue first on the cellular level, considering how activation of T-type Ca2+ channels in nonREM sleep may promote either long-term depression or long-term potentiation, as well as how cellular events of REM sleep may influence these processes. We then consider how synchronization of neuronal activity in thalamocortical and hippocampal–neocortical networks in nonREM sleep and REM sleep could promote differential strengthening of synapses according to the degree to which activity in one neuron is synchronized with activity in other neurons in the network. Rather than advocating one specific cellular hypothesis, we have intentionally taken a broad approach, describing a range of possible mechanisms whereby sleep may facilitate synaptic plasticity on the cellular and/or network levels. We have also provided a general review of evidence for and against the hypothesis that sleep does indeed facilitate learning, memory, and synaptic plasticity.

Abbreviations: AP, action potential; BDNF, brain-derived neurotrophic factor; CaM, Ca2+-calmodulin; CaMKII, CaM kinase II; CICR, Ca2+-induced Ca2+ release; CREB, cyclic AMP response element-binding protein; Ih, hyperpolarization-activated cation channel; IP3/DAG, inositol-triphosphate/diacylglycerol; LGN, lateral geniculate nucleus; LTD, long-term depression; LTP, long-term potentiation; MD, monocular deprivation; mGlu, metabotropic glutamate receptor; NGF, nerve growth factor; NO, nitric oxide; nNOS, neuronal nitric oxide synthase; NonREM, non-rapid-eye-movement; P, postnatal day; PCR, polymerase chain reaction; PET, positron emission tomography; PGO, ponto-geniculo-occipital; PSP, postsynaptic potential; REM, rapid-eye-movement; RSD, REM-sleep deprivation; SD, sleep deprivation; SS–PS, transition from nonREM sleep to REM sleep; STDP, spike-timing-dependent plasticity; VGCCs, voltage-gated Ca2+ channels

Article Outline

1. Introduction
2. The neurobiology of sleep and waking
3. Cellular and molecular mechanisms of synaptic plasticity

3.1. Long-term potentiation (LTP)
3.2. Long-term depression (LTD)
3.3. Spike-timing-dependent plasticity (STDP)
3.4. Retrograde signaling in synaptic plasticity

4. Evidence for a link between sleep and synaptic plasticity

4.1. Learning, memory, and sleep

4.1.1. Learning and REM-sleep augmentation
4.1.2. Sleep deprivation and learning

4.2. Neurochemical changes in sleep

4.2.1. Sleep and RNA/DNA synthesis
4.2.2. Sleep and gene expression
4.2.3. Sleep and protein synthesis

4.3. Reactivation of neuronal activity patterns in sleep
4.4. Sleep, sleep deprivation, and synaptic plasticity
4.5. Sleep and developmentally regulated synaptic plasticity

5. Facilitating synaptic plasticity on the cellular level

5.1. Ca2+ influx in sleep and synaptic plasticity
5.2. T-type Ca2+ channels and LTD
5.3. T-type Ca2+ channels and LTP
5.4. Cellular events of REM sleep and synaptic plasticity

6. Facilitating synaptic plasticity on the network level

6.1. Synchronized neuronal activity in nonREM sleep
6.2. Synchronized neuronal activity in REM sleep
6.3. Network-level models of sleep and synaptic plasticity

6.3.1. Thalamocortical interactions
6.3.2. Hippocampal–neocortical interactions

6.3.2.1. Two-stage models of hippocampal functioning

6.4. General evaluation of network-level models

7. Summary and conclusions

7.1. Facilitation of synaptic plasticity as the primary function of sleep
7.2. Future directions

References

Corresponding Author Contact InformationCorresponding author. Tel.: +1-716-375-2564; fax: +1-716-375-7618.

1 Co-corresponding author. Tel.: +1-215-746-0388.